Thromboembolic Disease Flashcards
Red thrombus
Fibrin-rich with a lot of red blood cells, occurs in veins
White thrombus
Platelet rich, in arteries
Prothrombotic factors that lead to thrombosis
Endothelial injury, abnormal blood flow, hypercoagulability or hypofibrinolysis
Drug classes for thromboembolic diseases
Systemic anticoagulants, antithrombotic drugs, fibrinolytic drugs
Systemic anticoagulants
Heparin, warfarin, rivaroxaban, bivalirubin, dabigatran
Reperfusion injury
Bad remnants from occlusion can shower tissue and cause injury
Heparin mechanism
Accelerates action of antithrombin III (ATIII)
Antithrombin III
Inhibits activated clotting factors through thrombin and (Xa they will remain bound and inactive)
Properties of heparin
Highly negatively charged, from mast cells
Uses for heparin
Initial treatment of thrombosis and thromboembolic diseases
Onset of heparin
Rapid, useful as an acute anticoagulant
What heparin does not do
Fibrinolysis
Adverse effects of heparin
Bleeding tendencies, thrombocytopenia, monitor with aPTT o use protamine sulfate in overdoses
Enoxaparin
Low MW heparin; inactivates Xa but not thrombin
Benefits of enoxaparin over unfractioned heparin
Less bleeding tendencies, less risk of thrombocytopenia, longer half-life so you can give subcutaneously
Warfarin
Oral anticoagulant
Warfarin mechanism
Prevents vitamin K from being reduced so clotting factors are not activated, not effective until existing coagulation factors are used
Warfarin monitoring
International normalized ratio (INR)
Toxicities of warfarin
Bleeding tendencies, crosses placenta (heparin does not)
Rivaroxaban
Directly inactivates factor Xa, nothing else
Uses for rivaroxaban
Prevention of stroke from atrial fibrillation, prevent of deep venous thrombosis and pulmonary embolism
Bivalirudin
Inhibits only thrombin, from leeches and given intravenously, binds both active site and exosite
Dabigatran
Oral thrombin inhibitor that only binds the active site
Therapeutic targets of antithrombotic drugs
Collagen, thrombin, ADP, 5HT, TXA2, COX, cAMP, cGMP, Ca2+
Antithrombotic drugs
Aspirin, clopidogrel, prasugrel, ticagrelor, abciximab, eptifibatide
Aspirin
Most commonly used anti-platelet drug, irreversibly binds COX1
What aspirin prevents
Thrombus formation
What aspirin does not do
Lose existing thrombi
Adverse effects of aspirin
Ulcers, renal damage, bleeding
Clopidogrel, prasugnel, ticagrelor
P2Y12 receptor antagonists so ADP cannot bind other platelets; some have to be activated by P450 enzymes, all are orally available and fairly safe
Glycoprotein IIb/IIIa
Receptor on surface of platelets for fibrinogen, anchors platelets together
Abciximab
Fab fragment of monoclonal antibody against IIb/IIIa receptor; irreversibly inhibits the receptor so platelets can’t aggregate
Toxicity of abciximab
Bleeding tendencies
Eptifibatide
Peptide that reversible inhibits the IIb/IIIa receptor, with similar adverse events as abciximab
Fibrinolytic drugs
Alteplase, tenecteplase
Alteplase
TPA, activates plasmin, short half-life
Toxicity of alteplase
Bleeding tendencies
Tenecteplase
Variant of TPA with less bleeding tendencies and longer half-life
